The broad goals of the research proposed in this application are directed toward gaining knowledge of the molecular reactions essential in several of adenovirus' pathogenic processes: acute pneumonia, latent or persistent infections, and cellular transformation. To approach these goals the following specific aims will be pursued: 1) Identification of the gene functions essential for pathogenesis of pneumonia in an animal model that pathologically is similar to that in humans, i.e., infection of the cotton rat; 2) Study of the mechanisms of the establishment of persistent infections of human T-4 lymphocytes; and 3) Investigate the mechanism by which the early regions 1a and 1b induce and maintain cellular transformation. One other specific aim will also be followed: Complete the characterization of newly isolated conditionally lethal, temperature-sensitive mutants of the E2a DNA-binding protein to attain better understanding of the several functions of this protein.